Ceftriaxone Attenuated Anxiety-Like Behavior and Enhanced Brain Glutamate Transport in Zebrafish Subjected to Alcohol Withdrawal.

Chronic and/or excessive consumption of alcohol followed by reduced consumption or abstention can result in Alcohol Withdrawal Syndrome. A number of behavioral changes and neurological damage result from ethanol (EtOH) withdrawal. Ceftriaxone (Cef) modulates the activity of excitatory amino acid transporters by increasing their gene expression. Zebrafish are commonly used to study alcohol exposure. The aim of this study was to evaluate the influence of Cef (100 µM) on behavior patterns, glutamate transport activity, and oxidative stress in zebrafish brains subjected to EtOH (0.3% v/v) withdrawal. The exploratory tests using Novel tank showed that EtOH withdrawal promoted a decrease in the time spent and number of entries of in the bottom displaying an anxiety-like behavior. In contrast, treatment with Cef resulted in recovery of exploratory behavioral patterns. Ceftriaxone treatment resulted in increased glutamate uptake in zebrafish subjected to EtOH withdrawal. Furthermore, EtOH withdrawal increased reactive species, as determined using thiobarbituric acid and dichlorodihydrofluorescein assays. Treatment with Cef reversed these effects. Ceftriaxone promoted a significant reduction in brain sulfhydryl content in zebrafish subjected to EtOH withdrawal. Therefore, Cef treatment in conjunction with EtOH withdrawal induced anxiolytic-like effects due to possible neuromodulation of glutamatergic transporters, potentially through mitigation of oxidative stress.